载血卟啉单甲醚中空金纳米球的光热光动力联合抗肿瘤研究  

Study on Photothermal and Photodynamic Antitumor Activity of Hollow Gold Nanospheres Coated Hematoporphyrin Monomethyl Ether

作　　者：李娜 游剑[1] LI Na;YOU Jian(College of Pharmaceutical Sciences,Zhejiang University,Hangzhou 310058,China;Hangzhou Dajiangdong Hospital,Hangzhou 311225,China)

机构地区：[1]浙江大学药学院,杭州310058 [2]杭州市大江东医院,杭州311225

出　　处：《中国现代应用药学》2020年第21期2617-2624,共8页Chinese Journal of Modern Applied Pharmacy

摘　　要：目的设计基于中空金纳米球(hollow gold nanospheres, HAuNS)的新型纳米给药系统(HMME-PEI-HAuNS),在近红外光照射下研究其同步光热光动力联合抗肿瘤作用。方法以钴纳米粒为模板制备HAuNS,将血卟啉单甲醚(hematopor phyrinmonomethylether,HMME)通过枝状聚乙烯亚胺[poly(ethyleneimine),PEI]装载到HAuNS表面,形成纳米给药系统(HMME-PEI-HAuNS);采用核磁共振氢谱、红外光谱、紫外光谱分析对HMME-PEI-HAuNS进行结构确证。建立荷瘤SKOV3小鼠模型,通过荧光活体成像仪考察其体内分布情况。将对肿瘤细胞表面EphB4受体具有特异性亲和力的靶向多肽TNYL修饰于其表面以增强该纳米体系的靶向性,用核染试剂Hoechst染色SKOV3细胞,在激光共聚焦显微镜下观察细胞内的荧光强度,用MTT比色法进行细胞毒性评价。结果 HAuNS能对HMME进行成功装载,装载率达(63.4?5.2)%。由于肿瘤的高渗透长滞留效应,HMME-PEI-HAuNS较游离HMME和HMME-PEI胶束在肿瘤部位有更多的累积量和更长的滞留时间,累计效率约为1.6%。荧光定量统计显示在TNYL多肽的介导下纳米球的靶向性更高,在808 nm激光照射下,TNYL-HMME-PEI-HAuNS发挥光热和光动力协同作用产生强大的肿瘤杀伤作用,在高浓度时,细胞存活率<10%。结论主动靶向纳米球(TNYL-HMME-PEI-HAuNS)在808 nm近红外光照射下具有较强的光热光动力联合抗肿瘤作用。OBJECTIVE To design a novel nanoparticle delivery system(HMME-PEI-HAuNS) based on hollow gold nanospheres(HAuNS), and to investigate the photothermal and photodynamic antitumor activity under the illumination of near-infrared light. METHODS HAuNS were prepared by a redox reaction using cobalt nanoparticles as a template. Hematopor phyrin monomethylether(HMME) was loaded on the surface of HAuNS via poly(ethylene imine)(PEI) as a linker to form a final nanoparticle delivery system(HMME-PEI-HAuNS). The structure of HMME-PEI-HAuNS was confirmed by NMR, IR and UV spectra. A tumor model of SKOV3 in mice was established and the biodistribution of HMME-PEI-HAuNS was investigated by fluorescence in vivo imager. Targeting peptide with specific affinity for tumor cell surface EphB4 receptors TNYL was further modified to enhance the tumor-targeting accumulation of the nanosystem. SKOV3 cells were stained with Hoechst, and the fluorescence intensity in the cells was observed using a laser confocal microscope. Cytotoxicity was evaluated by MTT colorimetry. RESULTS The HMME was successfully loaded in HAuNS with a rate of(63.4?5.2)%. Due to the enhanced permeability and retention effect of tumor, HMME-PEI-HAuNS had more accumulation and longer retention time in the tumor site than free HMME and HMME-PEI micelles, and the cumulative efficiency was about 1.6%. It was found that the targeting of nanosphere was significantly higher under the mediation of TNYL polypeptides. Under 808 nm laser irradiation, TNYL-HMME-PEI-HAuNS played a synergistic effect of photothermal and photodynamic therapy, inducing a powerful tumor cell killing, and the cell survival rate was less than 10% at high concentrations. CONCLUSION Active targeting nanosphere(TNYL-HMME-PEI-HAuNS) have strong photothermal and photodynamic antitumor effect under 808 nm NIR irradiation.

关 键 词：中空金纳米球 血卟啉单甲醚 近红外光 光热疗法 光动力疗法 肿瘤细胞 

分 类 号：R944[医药卫生—药剂学]